title: Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha 1-antichymotrypsin from serum.
abstract: OBJECTIVE
  To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP).
  
  
  METHODS
  We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis.
  
  
  RESULTS
  Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F concentrations in serum. Removal of the prostate resulted in a rapid, biexponential elimination of PSA-F from serum, corresponding to a mean initial (alpha) half-life of 0.81 hours and a mean terminal (beta) half-life of 13.9 hours. Serum PSA-ACT concentrations decreased by 20% to 40% immediately after removal of the gland; the elimination after surgery was slow and nonexponential, corresponding to a mean rate of 0.8 ng/mL/day. The elimination of PSA-T reflects a combination of the elimination patterns for PSA-F and PSA-ACT.
  
  
  CONCLUSIONS
  The main proportion of PSA-F is rapidly eliminated from serum, possibly by glomerular filtration. PSA-F released during surgery did not form complexes with ACT, as suggested by the lack of PSA-ACT elevation in serum. The size (approximately 90 kDa) and the extensive in vitro stability of the PSA-ACT complex prevents renal clearance. The nonexponential elimination of the PSA-ACT complex is evidence of a capacity-limited process (e.g., metabolic transformation).
authors.affiliation: Department of Urology, University Hospital, Malmö, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Björk
authors.forename: B
authors.initials: B
authors.lastname: Ljungberg
authors.forename: T
authors.initials: T
authors.lastname: Piironen
authors.forename: P A
authors.initials: PA
authors.lastname: Abrahamsson
authors.forename: K
authors.initials: K
authors.lastname: Pettersson
authors.forename: A T
authors.initials: AT
authors.lastname: Cockett
authors.forename: H
authors.initials: H
authors.lastname: Lilja
mesh_terms: D000368:Aged; D006801:Humans; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy; D013997:Time Factors; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
chemical_list: D000514:alpha 1-Antichymotrypsin; D017430:Prostate-Specific Antigen